Kim F J, Moore E E, Moore F A, Koike K, Carl V S, Banerjee A
Department of Surgery, Denver General Hospital, CO 80204.
Surgery. 1994 Aug;116(2):262-6; discussion 267.
We have previously shown that platelet-activating factor (PAF) primes polymorphonuclear neutrophils (PMNs) for superoxide generation and, concurrently, increases CD11/CD18 receptor expression; both events appear central to the pathogenesis of postinjury multiple organ failure. Recently, the counterinflammatory role of the neuroendocrine response to trauma has been emphasized, and, specifically, beta-adrenergic stimulation has been found to inhibit PMN activation.
Normal human PMNs were primed with PAF (10(-9) mol/L for 5 minutes) or pretreated with beta-receptor stimulation (isoproterenol, 10(-7) mol/L) or adenylate cyclase (AC) activation (forskoklin, 10(-7) mol/L) for 5 minutes and then primed with PAF. Superoxide generation in response to N-formyl-methionyl-leucyl-phenylalanine (10(-6) mol/L) was measured by superoxide dismutase inhibitable reduction of cytochrome C and CD18 expression determined by flow cytometry.
PAF primed PMNs for superoxide generation (229.5 +/- 42.3 nmol/10(6) cells/min versus 18.7 +/- 6.5), whereas pretreatment with beta-adrenoreceptor stimulation (112.9 +/- 20.6) or AC activation (115.3 +/- 12.6) dramatically attenuated this process (p < 0.0001). PAF also enhanced CD18 expression (6.1 +/- 1.1 mean fluorescence intensity versus 10.3 +/- 2.3), but beta-adrenoreceptor stimulation (10.1 +/- 2.1) and AC activation (9.7 +/- 1.9) had no discernible effect.
PAF priming of PMNs for superoxide generation was inhibited by the beta-adrenergic signal transduction pathway, but CD18 expression was not regulated via this pathway.
我们先前已表明，血小板活化因子（PAF）可使多形核中性粒细胞（PMN）引发超氧化物生成，同时增加CD11/CD18受体表达；这两个事件似乎在损伤后多器官功能衰竭的发病机制中起核心作用。最近，创伤的神经内分泌反应的抗炎作用得到了强调，具体而言，已发现β-肾上腺素能刺激可抑制PMN活化。
正常人类PMN用PAF（10⁻⁹mol/L，处理5分钟）引发，或先用β受体刺激（异丙肾上腺素，10⁻⁷mol/L）或腺苷酸环化酶（AC）激活（福斯可林，10⁻⁷mol/L）预处理5分钟，然后用PAF引发。通过超氧化物歧化酶抑制细胞色素C的还原测量对N-甲酰甲硫氨酰亮氨酰苯丙氨酸（10⁻⁶mol/L）的反应中超氧化物的生成，并通过流式细胞术测定CD18表达。
PAF使PMN引发超氧化物生成（229.5± 42.3 nmol/10⁶细胞/分钟，而未处理组为18.7± 6.5），而用β-肾上腺素能受体刺激（112.9± 20.6）或AC激活（115.3± 12.6）预处理可显著减弱此过程（p<0.0001）。PAF还增强了CD18表达（平均荧光强度为6.1± 1.1，而未处理组为10.3± 2.3），但β-肾上腺素能受体刺激（10.1± 2.1）和AC激活（9.7± 1.9）没有明显影响。
β-肾上腺素能信号转导途径抑制了PAF引发PMN生成超氧化物，但CD18表达并非通过此途径调节。
